The United States of America, As Represented by the Secretary, Department of Health and Human Services

Yale University

Icahn School of Medicine at Mount Sinai

Sri International

The Cooper Health System

University System of Maryland

Carlos A Zarate

Ruin Moaddel

Craig J Thomas

Dennis S Charney

John H Krystal

Husseini K Manji

Todd Gould

Panos Zanos

Sanjay J Mathew

Irving William Wainer

Marc C Torjman

Michel Bernier

Patrick Joseph Morris

Mary Jean Tanga

Michael E Goldberg

The disclosure provides a method for synthesizing free base foams of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal foams of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

Crystal forms and methods of synthesis of (2R, 6R)-hydroxynorketamine and (2S, 6S)-hydroxynorketamine

The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. (2R,6R)-hydroxynorketamine The disclosure also provides novel ketamine metabolite prodrugs. The disclosure provides methods of treating, bipolar depression, major depressive disorder, neuropathic and chronic pain, including complex regional pain synthetic pain disorder (CRPD) by administering a purified ketamine metabolite or a ketamine metabolite prodrug directly to patients in need of such treatment.

Use of (2R, 6R)-hydroxynorketamine, (S)-dehydronorketamine and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine in the treatment of depression and neuropathic pain

The disclosure provides pharmaceutical preparations containing (2R,6R)-hydroxynorketamine, or (R)- or (S)-dehydronorketamine, or other stereoisomeric dehydro or hydroxylated ketamine metabolite. (2R,6R)-hydroxynorketamine The disclosure also provides novel ketamine metabolite prodrugs. The disclosure provides methods of treating, bipolar depression, major depressive disorder, neuropathic and chronic pain, including complex regional pain disorder (CRPS) by administering a purified ketamine metabolite or a ketamine metabolite prodrug directly to patients in need of such treatment. 

Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (&#x3e;2 years).

Intranasal administration of ketamine to treat depression

Methods for treating suicidal ideation

Growing community of inventors

Rockville, MD, United States of America

Carlos A Zarate